title: Oxidized low-density lipoprotein induces inflammatory responses in cultured human mast cells via Toll-like receptor 4.
abstract: OBJECTIVE
  Oxidized low-density lipoprotein (ox-LDL) is a powerful atherogen. Toll-like receptor 4 (TLR4) has a pathophysiological role in regulating inflammatory responses and atherosclerosis. Mast cells can infiltrate into the atheromatous plaque and secrete various pro-inflammatory cytokines, which significantly amplify the atherogenic processes and promote plaque vulnerability. Small interfering RNA (siRNA) is an effective method to silence the target genes. We evaluated whether ox-LDL-induced inflammation depended in part on the activation of TLR4-dependent signaling pathways in a cultured human mast cell line (HMC-1).
  
  
  METHODS
  HMC-1 cells were cultured, and treated with ox-LDL, TLR4-specific siRNA, or inhibitors of phosphorylation of mitogen-activated protein kinase (MAPKs), and nuclear factor-κB (NF-κB), a critical mediator of inflammation. The expression of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6) was measured subsequently.
  
  
  RESULTS
  Ox-LDL increased the expression of TLR4 and secretion of MCP-1, TNF-α and IL-6. Moreover, ox-LDL stimulated the translocation of NF-κB, from the cytoplasm to nucleus. Additionally, phosphorylation of MAPK was greatly increased. These ox-LDL-induced alterations were significantly attenuated by pretreatment with TLR4-specific siRNA.
  
  
  CONCLUSIONS
  Ox-LDL induced inflammatory responses in cultured HMC-1 cells including NF-κB nuclear translocation and phosphorylation of MAPKs, a process mediated in part by TLR4.
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital, Xi'an Jiaotong University School of Medicine, Xi'an, Shaanxi, China. mengzhenihao@163.com
authors.forename: Zhe
authors.initials: Z
authors.lastname: Meng
authors.forename: Chao
authors.initials: C
authors.lastname: Yan
authors.forename: Qian
authors.initials: Q
authors.lastname: Deng
authors.forename: Xin
authors.initials: X
authors.lastname: Dong
authors.forename: Zong-Ming
authors.initials: ZM
authors.lastname: Duan
authors.forename: Deng-Feng
authors.initials: DF
authors.lastname: Gao
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Niu
mesh_terms: D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D018932:Chemokine CCL2; D018836:Inflammation Mediators; D015850:Interleukin-6; D008077:Lipoproteins, LDL; D016328:NF-kappa B; D034741:RNA, Small Interfering; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases